ASEPTIC TECHNOLOGIES FILLING SOLUTIONS SAFER & EASIER

Transcription

1 ASEPTIC TECHNOLOGIES FILLING SOLUTIONS SAFER & EASIER 2013

2 CLOSED VIAL TECHNOLOGY FOR INJECTABLES 1. Is a ready-to-fill vial 2. Is an aseptic fill and finish equipment Closed Vial Technology 3. Offers key advantages: SAFER for the patient EASIER for the manufacturer 4. Has been fully validated for aseptic filling 5. Has a product approved by EMA for all European countries. Core Technology licensed from MedInstill

3 ASEPTIC FILLING IS A COMPLEX PROCESS GLASS VIAL FILLING vials stoppers Is it possible to make it more simple?

4 ASEPTIC FILLING STILL RISKY INFECTION BY CONTAMINATED DRUGS 200,000 infections per year, i.e. 1/100,000 injections GLASS RELATED RECALLS 150 (Mio unit doses) i.e. 2% of all injections in the US Source: Joyce Bloomfield, Executive Director at Merck Sharp & Dohme in The Gold Sheet, May , Germany : death of 3 children due to cracks in glass bottles Can so many accidents be avoided?

5 Easier Safer A new Concept

6 FILL AND CLOSE A NEW CONCEPT KEY STEPS THE CLOSED VIAL A polymer vial (not glass) Supplied - Clean & pyrogene free - Closed & secure - Sterile (Gamma irradiated) Received Ready-to-fill How to fill it, as it is closed?

7 FILL AND CLOSE A NEW CONCEPT KEY STEPS A SPECIAL NEEDLE TO PIERCE THE STOPPER Pencil tip, 2 to 3.1 mm Sharp edges to make a clear cut in the stopper elastomer

8 FILL AND CLOSE A NEW CONCEPT KEY STEPS THE NEEDLE ENTERS INTO THE VIAL No coring Very low particles (measured twice lower than in glass vials)

9 FILL AND CLOSE A NEW CONCEPT KEY STEPS FILLING Lateral injection of the liquid Side grooves to avoid over-pressure during filling

10 FILL AND CLOSE A NEW CONCEPT KEY STEPS NEEDLE WITHDRAWAL Needle wiping by the stopper Needle withdrawal

11 FILL AND CLOSE A NEW CONCEPT KEY STEPS 2 mm THE STOPPER NATURALLY RECLOSES Tight contact of the lips of the piercing trace > 95% of the vials already resist to dye test 2mm Cut in the stopper

12 FILL AND CLOSE A NEW CONCEPT KEY STEPS A LASER FOR STOPPER RE-SEALING Laser in safe mode 980nm infrared 6mm, flat top Laser energy distribution

13 FILL AND CLOSE A NEW CONCEPT KEY STEPS STOPPER RE-SEALING One second laser shot Laser energy is absorbed by the stopper material No effect on the product in the vial (no t change) 100% 80% 60% 40% % 20% 0% Depth (mm)

14 FILL AND CLOSE A NEW CONCEPT KEY STEPS STOPPER INTEGRITY IS RESTORED Stopper re-sealed on at least 0.4mm Validation: welding resists to minimum 2.5 bars 2mm Cut in the stopper

15 FILL AND CLOSE A NEW CONCEPT KEY STEPS CAPPING PE cap Fixed by snap-fit Flip away

16 FILL AND CLOSE A NEW CONCEPT KEY STEPS SUMMARY SUPPLIED CLEAN, CLOSED & STERILE FILLING THROUGH THE STOPPER LASER RE-SEALING OF THE STOPPER CAPPING BY SNAP-FIT Simply Safer!

17 CLOSED VIAL TECHNOLOGY VS. GLASS VIAL FILLING GLASS VIAL FILLING vials stoppers CLOSED VIAL FILLING In Grade B (ISO 7) In Grade C (ISO 8) Lean manufacturing & increased safety

18 CLOSED VIAL TECHNOLOGY KEY ADVANTAGES THE FILLING PROCESS Eliminates the most complex steps of aseptic filling: no WFI washing no hot-air tunnel no stopper sterilization no siliconization no stoppering no aluminium crimping Limits the risk of contamination as the sterile vial remains always closed (2 logs reduction) Limits the risk of batch rejection thanks to process simplification Has lower environmental impact (-20%) compared to glass vial Simplifies and secures operations

19 The Vials

20 CLOSED VIAL RANGE 1ml 2ml 6ml 10ml 20ml 50 ml A complete range of ready-to-fill vials

21 CLOSED VIAL DESCRIPTION FLIP AWAY CAP TOP RING Ensures sterility assurance level of the piercing area Ensures closure integrity STOPPER Made of Thermoplastic Elastomer (TPE) Allows laser resealing after filling VIAL BODY Made of Cyclo-olefin co-polymer (COC) Contains volume from 0.2 to 50ml BOTTOM RING Ensures mechanical stability of small vials Isolator at item level

22 CLOSED VIAL BEHAVIOR AT VERY LOW TEMPERATURE RESISTS TO STORAGE IN LIQUID NITROGEN Closure integrity TPE stopper ensures uncompromised closure integrity. Visual aspect Polymer vial body resists to extremely low temperature storage. Crystal Closed Vials particularly suitable and widely used for cryogenic storage of injectables

23 CLOSED VIAL VIAL MANUFACTURING Healthcare 2 sites in operation: - Neuenburg (DE) - Offranville (FR) Fully automated

24 VALIDATION MASTER PLAN CONTAINER MATERIALS Reference Irradiated COC vial body Irradiated TPE stopper USP <87> In vitro cytotoxicity Pass Pass USP <88> In vivo biocompatibility Pass Pass Comment USP Class VI USP <661> Physico chemical tests Pass N.A. EP Polyolefins Pass N.A. NIR Chemical change after laser (and e beam) N.A. Pass No change Extractables Done Done For leachables

25 VALIDATION MASTER PLAN ASSEMBLED CONTAINER Reference Result Comment USP <788> Particle test Full process Multiple piercing with the same needle USP <381> & EP Elastomeric closure Extractables and leachables Vial cleanness (Endotoxins and bio burden) Pass Pass Pass Pass Pass 2 x less 5 & 10 micron particles, compared to glass vials Permeability Water loss Oxygen Low temperature storage 20 c 80 c liquid nitrogen Pass Done Pass Pass Pass According to ICH Ageing in ICH conditions Pass 4 years until now

26 The filling lines

27 CRYSTAL FILLING LINES FOR LAB S INSTALLATION IN GRADE B, C or D

28 CRYSTAL L1 ROBOT LINE PRODUCTION STEPS FULLY AUTOMATED SMALL BATCH PRODUCTION 1. Filling 2. Re-sealing 3. Capping Robot head perfoms all operations

29 CRYSTAL PRODUCTION LINES INSTALLATION IN GRADE B or C A filling line for each of your needs

30 VALIDATION MASTER PLAN FILLING LINE TECHNOLOGIES TOPICS VALIDATIONS STUDIES STATUS Laser resealing Filling Media fill Absorption coefficient No change of stopper composition Temperature increase On stopper surfaces Inside the vial Resealing specifications Resistance of the weld Accuracy of filling : 10µL/1ml More than vial filled. (incl in the workshop) No contaminated vial until now Done Done Done* Done Done Done Done * on test equipment Supports your product approval

31 CRYSTAL TECHNOLOGY USERS Bilthoven, Netherlands Warren, NJ, USA San Carlos, CA, USA Geneva, Switzerland Chennai, India Walkersville, MD, USA Visp, Switzerland Singapore Martinsried, Germany México D.F., México Haifa, Israel Allendale, NJ, USA Brussels, Belgium Crystal equipment Head quarters Representation office SYNFLORIX pediatric vaccine is approved by EMA in the Closed Vial for all European countries Already EMA approved

32 CLOSED VIAL TECHNOLOGY FDA s POSITION Certain modern manufacturing designs (isolators 1 and "closed vial" filling) afford isolation of the aseptic process from microbiological contamination risks (e.g., operators and surrounding room environment) throughout processing. 1/ This does not apply to RABS (Restricted Access Barrier Systems) htm In February 2012, Aseptic Technologies presented the Closed Vial Technology to ~80 inspectors of the FDA, Office of Manufacturing and Product Quality. During that training session, in depth information was presented about the vial, the equipment and the Validation Master Plan.

33 Conclusion

34 CLOSED VIAL TECHNOLOGY A SIMPLE 3 STEP PROCESS PLASTIC MOLDER IRRADIATION SITE PHARMA SITE Vial aseptically molded and closed Vial sterilized Vial filled, laser re-sealed and capped The first ready-to-fill closed vial which really minimizes the risk of contamination Let s focus on your product!

35 CLOSED VIAL TECHNOLOGY THE CHALLENGE KEY ADVANTAGES FOR WHOM? WHY? SAFER For your regulatory For your supply chain Top-class sterility assurance level thanks to a closed ready-to-fill vial Product secured inside an unbreakable and unique container EASIER For your manufacturing For your QA/QC For your marketing Lean manufacturing leading to lower investment and operating costs Simple and dry process reducing initial and regular validation work Appreciated by practitioners => boost sales The SAFE and EASY solution

36 CLOSED VIAL TECHNOLOGY KEY APPLICATIONS A technology recommended for products like All biologicals & vaccines (aseptic process) Cell therapy (low temperature) Cancer therapy (unbreakable & always closed) Closed Vial Technology High value (unbreakable & no-counterfeitable) A technology recommended for projects like Investment in new capacities (less CAPEX) Move to injectables (safer & easier process) Need to differentiate (competitive advantages)

37 Simply Safer! Patrick BALERIAUX CEO PARC SCIENTIFIQUE CREALYS Rue Camille Hubert 7 B-5032 Gembloux Belgium T F patrick.baleriaux@aseptictech.com

38 Copyright by Aseptic Technologies S.A., Gembloux, Belgium. All rights reserved. All text, images, graphics, animation, videos, and other materials on this document are subject to the copyright and other intellectual property rights of Aseptic Technologies S.A. These materials may not be reproduced, distributed, modified, reposted or translated in any form or by any means without the prior written permission of Aseptic Technologies S.A. The status of the information, specifications and illustrations in this presentation is indicated by the date given below. Aseptic Technologies S.A. reserves the right to make changes to the technology, features, specifications, and design of the equipment without notice. Status: November 2012, Aseptic Technologies S.A., Gembloux, Belgium

39 ASEPTIC TECHNOLOGIES UK NL Created in 2002 as a spin-out of GSK Biologicals. Head quarter in the South-East of Brussels, Belgium. D 4,000 m 2 facility, including m 2 GMP approved Crystal Filling Suite - 40 m 2 Grade D laboratory for development F Representation Office in Raleigh, NC, USA. Since 2011, member of the SKAN Group ISO-9000 certified. Devices & filling kits Filling line eng. & manufacturing Development Lab & Lyo. EMA GMP approved DMF at the FDA An innovating company

40 THE COMPANY MAIN MILE STONES The concept is presented to FDA Validation results presented to FDA Synflorix filled for stabs Synflorix in Crystal approved by EMA Founded by GSK Bio Filling suite GMP approved First media fill is a success First 2 equip. outside of GSK First equip. in India Prototype of small vial manufact. Small vial manufact Industrial scale Large vial manufact. Pilote scale Large vial manufact. Industrial scale GSK 100% GSK 84% SRIW 16% GSK 19% SRIW 40% SKAN 41% Core technology licensed from MedInstill

41 VALIDATION MASTER PLAN WATER VAPOR TRANSMISSION IN ICH CONDITIONS LOSS OF WATER - 2ML VIAL FILLED WITH 1.2ML mg 5% limit for stability at 3 months in accelerated condition* 40 C - 25%RH Accelerated 12.5% / year 30 C - 35%RH 5.5% / year 25 C - 60%RH accelerated 3.1% / year 2-8 C 0.2% / year -20 C Months *According to ICH; if exceeded, effect on product to be examined No concern regarding ICH Guidelines

42 FREEZE DRYING

43 LYOPHILIZATION WITH CRYSTAL PROCESS 1. Normal vial filled but not laser re-sealed 2. Penetray (funnel shape) placed in line on vial top before loading in the freeze dryer The tray is placed on the top

44 LYOPHILIZATION WITH CRYSTAL PROCESS 3. Lyo shelve moved down to push the penetray and reopens the piercing trace Lyo shelve 4. Lyophilization done through the piercing trace Individual penetrator pressed by the shelve The tray re-opens the piercing trace

45 LYOPHILIZATION WITH CRYSTAL PROCESS 5. Lyo shelve releases 6. Penetray withdraws thanks to stopper elasticity 7. Vial are laser re-sealed and capped The vials re-close

46 LYOPHILIZATION WITH CRYSTAL TEST RESULTS WITH EXCIPIENTS EXCIPIENTS TESTED AND OBSERVATIONS Lactose 5 % : Lactose 10 % : Sucrose 5 % : Sucrose 10% : Multiple sizes : Lyophilization performed using the same cycles as for glass vials High quality of cakes Vials are closed during transfer and loading Good vial stability during loading No vial breakage No stopper sticking on the shelves Multiple advantages over glass vials